Deep targeted sequencing reveals the diversity of TRB-CDR3 repertoire in patients with preeclampsia

Hum Immunol. 2019 Oct;80(10):848-854. doi: 10.1016/j.humimm.2019.04.003. Epub 2019 Apr 6.

Abstract

Preeclampsia (PE) is one of the major causes of maternal and perinatal mortality worldwide. This study aimed to determine the immunological characteristics of PE patients and normal pregnancy at the T cell receptor beta-chain (TRB) level by using high-throughput sequencing. High-throughput sequencing was performed to analyze the expression of TRB-CDR3 in circulating T cells. T cells were isolated from 36 healthy pregnant women, 24 patients with severe PE, and 18 patients with moderate PE. Rearranged mRNA sequences were assigned to their germline V, D, and J counterparts, and translated into proper amino acids by the IMGT database. In general, PE samples had more TRB-CDR3 reads and types than those of normal pregnant woman in the circulation, but the mean number of TRB-CDR3 reads and unique TRB-CDR3 reads in severe group was lower than that in the moderate group. In PE patients, the V7_9 and V20_1 gene loci were more prevalent than in healthy pregnant women. In addition, 4 kinds of TRB-CDR3 peptides were found to be highly relevant to the pathogenesis of PE. Of them, peptides matched to herpes simplex virus antigen-specific T cells were much lower in PE samples.

Keywords: High-throughput sequencing; Immunological characteristics; Preeclampsia; TRB-CDR3 repertoire; The pathogenesis of PE.

MeSH terms

  • Adult
  • Amino Acid Sequence / genetics
  • Base Sequence / genetics
  • Complementarity Determining Regions / genetics*
  • Female
  • Genes, T-Cell Receptor beta / genetics*
  • Genetic Loci / genetics
  • Genetic Variation / genetics*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Multiplex Polymerase Chain Reaction / methods
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • T-Lymphocytes / immunology
  • Young Adult

Substances

  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell, alpha-beta